Abstract:
BACKGROUND:Huntington's disease (HD) is a devastating brain disorder with no effective treatment or cure available. The scarcity of brain tissue makes it hard to study changes in the brain and impossible to perform longitudinal studies. However, peripheral pathology in HD suggests that it is possible to study the disease using peripheral tissue as a monitoring tool for disease progression and/or efficacy of novel therapies. In this study, we investigated if blood can be used to monitor disease severity and progression in brain. Since previous attempts using only gene expression proved unsuccessful, we compared blood and brain Huntington's disease signatures in a functional context. METHODS:Microarray HD gene expression profiles from three brain regions were compared to the transcriptome of HD blood generated by next generation sequencing. The comparison was performed with a combination of weighted gene co-expression network analysis and literature based functional analysis (Concept Profile Analysis). Uniquely, our comparison of blood and brain datasets was not based on (the very limited) gene overlap but on the similarity between the gene annotations in four different semantic categories: "biological process", "cellular component", "molecular function" and "disease or syndrome". RESULTS:We identified signatures in HD blood reflecting a broad pathophysiological spectrum, including alterations in the immune response, sphingolipid biosynthetic processes, lipid transport, cell signaling, protein modification, spliceosome, RNA splicing, vesicle transport, cell signaling and synaptic transmission. Part of this spectrum was reminiscent of the brain pathology. The HD signatures in caudate nucleus and BA4 exhibited the highest similarity with blood, irrespective of the category of semantic annotations used. BA9 exhibited an intermediate similarity, while cerebellum had the least similarity. We present two signatures that were shared between blood and brain: immune response and spinocerebellar ataxias. CONCLUSIONS:Our results demonstrate that HD blood exhibits dysregulation that is similar to brain at a functional level, but not necessarily at the level of individual genes. We report two common signatures that can be used to monitor the pathology in brain of HD patients in a non-invasive manner. Our results are an exemplar of how signals in blood data can be used to represent brain disorders. Our methodology can be used to study disease specific signatures in diseases where heterogeneous tissues are involved in the pathology.
journal_name
Orphanet J Rare Disjournal_title
Orphanet journal of rare diseasesauthors
Mina E,van Roon-Mom W,Hettne K,van Zwet E,Goeman J,Neri C,A C 't Hoen P,Mons B,Roos Mdoi
10.1186/s13023-016-0475-2subject
Has Abstractpub_date
2016-08-01 00:00:00pages
97issue
1issn
1750-1172pii
10.1186/s13023-016-0475-2journal_volume
11pub_type
杂志文章abstract:BACKGROUND:We sought to understand the experiences of parents/caregivers of children with inherited metabolic diseases (IMD) in order to inform strategies for supporting patients and their families. We investigated their experiences regarding the management of disease, its impact on child and family life, and interacti...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-016-0548-2
更新日期:2016-12-07 00:00:00
abstract::Urea cycle disorders (UCDs) are inborn errors of ammonia detoxification/arginine synthesis due to defects affecting the catalysts of the Krebs-Henseleit cycle (five core enzymes, one activating enzyme and one mitochondrial ornithine/citrulline antiporter) with an estimated incidence of 1:8.000. Patients present with h...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
doi:10.1186/1750-1172-7-32
更新日期:2012-05-29 00:00:00
abstract:BACKGROUND:Niemann-Pick disease Type C1 (NPC1) is a rare progressive neurodegenerative disorder caused by mutations in the NPC1 gene. The pathological mechanisms, underlying NPC1 are not yet completely understood. Especially the contribution of glial cells and gliosis to the progression of NPC1, are controversially dis...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-017-0697-y
更新日期:2017-08-25 00:00:00
abstract::Xeroderma pigmentosum-Cockayne syndrome complex is a very rare multisystem degenerative disorder (Orpha: 220295; OMIM: 278730, 278760, 278780, 610651). Published information on XP-CS is mostly scattered throughout the literature. We compiled statistics related to symptom prevalence in XP-CS and have written a clinical...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
doi:10.1186/s13023-017-0616-2
更新日期:2017-04-04 00:00:00
abstract::Achondroplasia is the most common of the skeletal dysplasias that result in marked short stature (dwarfism). Although its clinical and radiologic phenotype has been described for more than 50 years, there is still a great deal to be learned about the medical issues that arise secondary to this diagnosis, the manner in...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
doi:10.1186/s13023-018-0972-6
更新日期:2019-01-03 00:00:00
abstract:BACKGROUND:Most patients with alpha-1 antitrypsin deficiency remain undiagnosed and therefore do not benefit from current therapies or become eligible for research studies of new treatments under development. Improving the detection rate for AATD is therefore a high priority for the Alpha-1 Foundation. A workshop was h...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
doi:10.1186/s13023-020-01352-5
更新日期:2020-04-19 00:00:00
abstract:BACKGROUND:Rare diseases can lead to a significant reduction in quality of life for patients and their families. Ensuring the patients voice is central to clinical decision making is key to delivering, evaluating and understanding the efficacy of therapeutic interventions. Patient reported outcome measures (PROMs) are ...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
doi:10.1186/s13023-018-0810-x
更新日期:2018-04-23 00:00:00
abstract:BACKGROUND:It is unknown whether the neonatal tetrahydrobiopterin (BH4) loading test is adequate to diagnose long-term BH4 responsiveness in PKU. Therefore we compared the predictive value of the neonatal (test I) versus the 48-h BH4 loading test (test II) and long-term BH4 responsiveness. METHODS:Data on test I (>199...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-016-0394-2
更新日期:2016-01-29 00:00:00
abstract::An amendment to this paper has been published and can be accessed via the original article. ...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,已发布勘误
doi:10.1186/s13023-020-01464-y
更新日期:2020-08-05 00:00:00
abstract:BACKGROUND:Acute hepatic porphyria (AHP) consists of three rare metabolic disorders. We investigated the risk of long-term sick leave, disability pension, and premature death in individuals with AHP compared to the general population. METHODS:In a nationwide cohort study from 1992 to 2017, records of 333 persons (tota...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-019-1273-4
更新日期:2020-02-21 00:00:00
abstract:BACKGROUND:Müllerian aplasia (MA) characterized by congenital loss of functional uterus and vagina is one of the most difficult disorders of female reproductive health. Despite of growing interest in this research field, the cause of the disorder for the majority of patients is still unknown. A recent report of partial...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-6-53
更新日期:2011-08-02 00:00:00
abstract:BACKGROUND:Hypophosphatasia (HPP) is a rare inborn error of metabolism that results from dysfunction of the tissue non-specific alkaline phosphatase enzyme. Its manifestations are extremely variable, ranging from early lethality to disease limited to the dentition. The disease is life-threatening when manifesting withi...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
doi:10.1186/s13023-018-0866-7
更新日期:2018-07-16 00:00:00
abstract:BACKGROUND:Purine nucleoside analogs (PNAs) are the recommended first-line treatment for patients with hairy cell leukemia (HCL), but they are associated with adverse events (AEs). Due to a lack of real-world evidence regarding AEs that are associated with PNAs, we used commercial data to assess AE rates, AE-related he...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-020-1325-9
更新日期:2020-02-13 00:00:00
abstract:BACKGROUND:The concept of individual burden, associated with disease, has been introduced recently to determine the "disability" caused by the pathology in the broadest sense of the word (psychological, social, economic, physical). Inherited ichthyosis belong to a large heterogeneous group of Mendelian Disorders of Cor...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-8-28
更新日期:2013-02-15 00:00:00
abstract::Cerebrotendinous xanthomatosis (CTX) OMIM#213700 is a rare autosomal-recessive lipid storage disease caused by mutations in the CYP27A1 gene; this gene codes for the mitochondrial enzyme sterol 27-hydroxylase, which is involved in bile acid synthesis. The CYP27A1 gene is located on chromosome 2q33-qter and contains ni...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
doi:10.1186/s13023-014-0179-4
更新日期:2014-11-26 00:00:00
abstract:BACKGROUND:The TRPV4 gene encodes a calcium-permeable ion-channel that is widely expressed, responds to many different stimuli and participates in an extraordinarily wide range of physiologic processes. Autosomal dominant brachyolmia, spondylometaphyseal dysplasia Kozlowski type (SMDK) and metatropic dysplasia (MD) are...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-6-37
更新日期:2011-06-09 00:00:00
abstract::Malignant mesothelioma is a fatal asbestos-associated malignancy originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the pericardium and the tunica vaginalis. The exact prevalence is unknown but it is estimated that mesotheliomas represent less than 1% of all cancers. Its...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
doi:10.1186/1750-1172-3-34
更新日期:2008-12-19 00:00:00
abstract:BACKGROUND:While extraocular muscles are affected early in myasthenia gravis (MG), but respond to treatment, we observe a high incidence of treatment-resistant ophthalmoplegia (OP-MG) among MG subjects with African genetic ancestry. Previously, using whole exome sequencing, we reported potentially functional variants w...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-019-1003-y
更新日期:2019-01-29 00:00:00
abstract:BACKGROUND:Thalassaemia is a potentially life-threatening yet preventable inherited hemoglobin disorder. Understanding local socio-cultural context and level of public awareness about thalassaemia is pivotal for selecting effective prevention strategies. This study attempted to assess knowledge and perceptions about th...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-020-1323-y
更新日期:2020-02-21 00:00:00
abstract:BACKGROUND:Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscle disorder, which is linked to the contraction of the D4Z4 array at chromosome 4q35. Recent studies suggest that this shortening of the D4Z4 array leads to aberrant expression of double homeobox protein 4 (DUX4) and causes FSHD. In a...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-8-55
更新日期:2013-04-05 00:00:00
abstract:BACKGROUND:Phenylketonuria (PKU) is an inherited metabolic disorder characterized by reduced activity of phenylalanine hydroxylase resulting in elevated blood phenylalanine (Phe) concentration. Despite some obvious ocular changes, the disorder has been poorly recognized by ophthalmologists. Neurophysiologic tests imply...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-020-01407-7
更新日期:2020-05-25 00:00:00
abstract:BACKGROUND:Cystinosis is a rare autosomal recessive disorder caused by intracellular cystine accumulation. Proximal tubulopathy (Fanconi syndrome) is one of the first signs, leading to end-stage renal disease between the age of 12 and 16. Other symptoms occur later and encompass endocrinopathies, distal myopathy and de...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-019-1271-6
更新日期:2020-02-26 00:00:00
abstract:BACKGROUND:The diagnosis of rare diseases poses a particular challenge to clinicians. This study analyzes whether patients' pain drawings (PDs) help in the differentiation of two pain-associated rare diseases, Ehlers-Danlos Syndrome (EDS) and Guillain-Barré Syndrome (GBS). METHOD:The study was designed as a prospectiv...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-020-01542-1
更新日期:2020-11-17 00:00:00
abstract:BACKGROUND:The objective of this study was to assess the potential impact of the implementation of multiple-criteria decision analysis (MCDA) on the Polish pricing and reimbursement (P&R) process with regard to orphan drugs. METHODS:A four step approach was designed. Firstly, a systematic literature review was conduct...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-016-0388-0
更新日期:2016-03-10 00:00:00
abstract:BACKGROUND:Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare disease, characterized by the massive accumulation of triglyceride (TG) in multiple tissues, especially skeletal muscle, heart muscle and the coronary artery. TGCV is caused by mutation of adipose triglyceride lipase, which is an essential molecule ...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-8-197
更新日期:2013-12-21 00:00:00
abstract:BACKGROUND:Glycogenosis type II or Pompe disease is an autosomal-recessive lysosomal storage disease due to mutations in the gene encoding acid alpha-glucosidase (GAA), an enzyme required for lysosomal glycogen degradation. The disease predominantly affects the skeletal and respiratory muscles but there is growing evid...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-9-17
更新日期:2014-02-05 00:00:00
abstract::Infantile cholestatic diseases can be caused by mutations in a number of genes involved in different hepatocyte molecular pathways. Whilst some of the essential pathways have a well understood function, such as bile biosynthesis and transport, the role of the others is not known. Here we report the findings of a clini...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/1750-1172-8-74
更新日期:2013-05-16 00:00:00
abstract::Pompe disease/glycogen storage disease type II, is a rare, lysosomal storage disorder associated with progressive proximal myopathy, causing a gradual loss of muscular function and respiratory insufficiency. Studies of patients with late-onset Pompe disease have used endpoints such as the 6-minute walking test (6MWT) ...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章,评审
doi:10.1186/1750-1172-8-160
更新日期:2013-10-12 00:00:00
abstract:BACKGROUND:Achondroplasia is the most common form of disproportionate short stature and might affect not only the quality of life of the affected child but also that of the parents. OBJECTIVES:We aimed to investigate the quality of life of children with achondroplasia from child- and parent perspective as well as the ...
journal_title:Orphanet journal of rare diseases
pub_type: 杂志文章
doi:10.1186/s13023-019-1171-9
更新日期:2019-08-09 00:00:00
abstract:UNLABELLED:Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genodermatosis with severe blistering. No curative treatment is available. Scientific data indicated that epigallocatechin-3-gallate (EGCG), a green tea extract, might improve the phenotype of RDEB patients. In a multicentre, randomized, crossover, ...
journal_title:Orphanet journal of rare diseases
pub_type: 信件,随机对照试验
doi:10.1186/s13023-016-0411-5
更新日期:2016-03-25 00:00:00